A Study to Evaluate the Feasibility of Screening Relatives of Patients Affected by Non-Syndromic Thoracic Aortic Diseases (ReST)

University of Leicester

Status: Unknown

Conditions: Screening; Genetic Disease; Aortic Aneurysm and Dissection

Treatments: Diagnostic Test: TTE; Other: Questionnaire; Diagnostic Test: MRI; Genetic: WES

Study type: Interventional

Funder types: Other

Identifiers

NCT03861741

0676

Details and patient eligibility

About

The primary hypothesis is that a tailored programme of genetic and imaging screening of first- and second-degree relatives of patients affected by non-syndromic forms of thoracic aortic diseases will identify individuals at risk of death from these conditions. These individuals would constitute specific population of patients, requiring dedicated imaging surveillance and/or earlier prophylactic aortic surgery.

Full description

Diseases involving the thoracic aorta (the major artery in the body) are a major health problem affecting an increasing number of people worldwide.

In particular, a group of these conditions termed Non-Syndromic Aortic Diseases (NS-TAD), can develop without any obvious symptoms or external features which prevents early identification. Unfortunately, if not treated, the aorta may enlarge and lead to dissection, a life-threatening medical emergency. For this reason, the investigators believe it might be helpful to investigate relatives of patients undergoing surgery for thoracic aortic disease to understand if there are tests that could help identify and treat this condition at the right time.

Therefore the investigators propose to conduct a feasibility study to identify the practical issues and challenges that would need to be overcome in order to perform a successful tailored genetic (by collecting a small blood sample) and imaging (with exams such as echocardiography and MRI) screening in such population of individuals.

Moreover, all participants will receive two questionnaires to ask their opinion about the study and to measure their levels of anxiety and depression, to judge whether and how this study has affected their emotional status.

The study will be carried out at the Department of Cardiovascular Sciences Glenfield Hospital, University Hospitals of Leicester NHS Trust.

Enrollment: 70 patients

Sex: All

Ages: 16+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. NS-TAD probands operated on (n=16).

2. FDR and SDR, aged 16 and above:

   1. At least two relatives willing to participate in the screening programme.
   2. Relatives able to understand English.

Exclusion criteria

1. Probands with syndromic aortopathies, including Marfan Syndrome, Loeys-Dietz Syndrome, Ehlers-Danlos Syndrome, Shprintzen-Goldberg syndrome, aneurysm-osteoarthritis syndrome, arterial tortuosity syndrome, and cutis laxa syndrome.
2. Probands with aortic lesions associated with trauma and infections.
3. Probands/relatives unable to give informed consent

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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70 participants in 1 patient group

Participants

Experimental group

Description:

All participants will be screened through complete clinical evaluations, genetic tests and imaging modalities (TTE and MRI) for the presence of newly Non Syndromic-Thoracic Aortic Diseases. Demographic and clinical data from all participants will be collected using case report forms, and by accessing their medical records. Data on imaging investigations will be obtained from TTE and MRI. Blood samples will be used for the purpose of isolation of genetic material and subsequent whole exome sequencing along with the analysis of selected loci. Additional citrated blood samples and plasma will be collected and stored for the potential analysis of circulating microvesicles and miRNA.

Treatment:

Genetic: WES

Diagnostic Test: MRI

Other: Questionnaire

Diagnostic Test: TTE